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Healthcare systems worldwide are struggling to find ways to fund the cost of innovative treatments such as gene therapies, regenerative medicine, and monoclonal antibodies (mAbs). As the world's best known mAbs are close to facing patent expirations, the biosimilars market is poised to grow with the hope of bringing prices down for cancer treatment and autoimmune disorders, however, this has yet to be realized. The development costs of biosimilars are significantly higher than their generic equivalents due to therapeutic equivalence trials and higher manufacturing costs. It is imperative that academics and relevant companies understand the costs and stages associated with biologics processing. This article brings these costs to the forefront with a focus on biosimilars being developed for Rheumatoid Arthritis (RA). mAbs have remarkably changed the treatment landscape, establishing their superior efficacy over traditional small chemicals. Five blockbuster TNFα mAbs, considered as first line biologics against RA, are either at the end of their patent life or have already expired and manufacturers are seeking to capture a significant portion of that market. Although in principle, market-share should be available, withstanding that the challenges regarding the compliance and regulations are being resolved, particularly with regards to variation in the glycosylation patterns and challenges associated with manufacturing. Glycan variants can significantly affect the quality attributes requiring characterization throughout production. Successful penetration of biologics can drive down prices and this will be a welcome change for patients and the healthcare providers. Herein we review the biologic TNFα inhibitors, which are on the market, in development, and the challenges being faced by biosimilar manufacturers. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis is an autoimmune disease with prevalence all over the world. Several therapeutics with different modes of action are available to deal with the disease but have failed to produce universal response leaving a large proportion of patients untreated. This is due to complex pathogenesis comprising a network of signaling pathways. By controlling one pathway, the pathogenesis continues through complementary pathways. Janus kinase and bruton's tyrosine kinase regulates a number of T-cell and B-cell mediated signaling pathways ranging from cytokine expression and antibody production to the bone resorption and cartilage destruction. We propose a dual trap to control this pathogenesis in the form of dual JAK3/BTK inhibitor. Using the computer-aided drug designing techniques, we developed dual JAK3 and BTK inhibitors based on quinoxaline derivatives which show appreciable dual inhibition in enzyme assays. To our knowledge, this is the first-ever report on dual JAK3/BTK inhibitors. [ABSTRACT FROM AUTHOR]